The histopathology and pathophysiology seen after perforant path stimulation are extremely similar to that seen in resected tissue from humans with temporal lobe epilepsy. A subset of GABAergic interneurons are lost in the effected hippocampus. The histopathology is restricted to the stimulated hippocampus making this area a likely site for seizure genesis or permissiveness. Perforant path-stimulated animals have a very low threshold for seizures which can be elicted reliably with kindling stimuli. This low threshold for seizure defines the epileptic brain. All of these factors make this model ideal for testing the anticonvulsant effect of genetically engineered GABA-producing cells. The new generation of inducible promoters which harness the control of a prokaryotic system of antibiotic responsive promoter elements are particularly promising. The system demonstrates remarkable fidelity with little adverse side effects which plague other inducible promoter systems. The controlling agent, tetracycline, has a well established history of being well tolerated in mammals. We will test: 1) whether controlled production of GABA from cells transplanted into the substantia nigra/VTA can suppress kindled seizures in animals with hippocampal sclerosis and 2) whether controlled expression of GABA from cells transplanted into the hippocampus can block the facilitated epileptogenesis seen after perforant path stimulation.